Synthesis of 1-methyl-2-hydroxy-3-oxatricyclo(5.2.0.0**4,9)nonane;novel intermediate compounds and reactions of said synthesis



United States Patent SYNTHESIS OF l-METHYL-Z-HYDROXY-S-0XATRI- CYCL0(5.2.0.0 )N0NANE; NOVEL INTERMEDI- ATE COMPOUNDS AND REACTIONS OF SAID SYNTHESIS Thomas W. Gibson, Cincinnati, Ohio, assignor to The Procter & Gamble Company, Cincinnati, Ohio, a corporation of Ohio No Drawing. Filed Dec. 16, 1966, Ser. No. 602,141

Int. Cl. C07d /32 US. Cl. 260-3462 2 Claims ABSTRACT OF THE DISCLOSURE The synthesis of l-methyl-2-hydroxy-3-oxatricyclo- [5.2.0.0 nonane and novel intermediates produced therein are disclosed. 1-methyl-2-hydroxy-3-oxatricyclo [5.2.0.0 -nonane is useful as a perfume.

This invention relates to the synthesis of 1-methyl-2- hydroxy-S-oxatricyclo[5.2.0.0 ]nonane and to novel intermediate compounds and reactions of said synthesis. More specifically, a four-step process starting with readily preparable cis-nopinol, through the sequential formation of the novel compounds cis-2-nopinyl nitrate, 8-nitroso cis-nopinol dimer, and 8-oximino-cis-nopinol, and resulting ultimately in the formation of 1-methyl-2-hydroxy-3- oxatricyclo[5.2.O.0 ]11onane has been discovered.

l-methyl-Z-hydroxy-3-oxatricyclo[5.2.O.0 ]nonane has an odor characterized as strong green-pithy camphoraceous and is useful in the perfume arts as described in detail hereinafter. This compound can be readily oxidized to l-methy1-2-oxo-3-oxatricyclo[5.2.0.0 ]nonane, a compound that is also useful in the perfume art as described in the co-pending US. patent application of Thomas W. Gibson and William F. Erman, Ser. No. 602,132, filed concurrently herewith. An alternative method of preparing 1-methyl-2-oxo-3-oxatricyclo[5.2.0.0 ]nonane is also disclosed in said co-pending application.

Accordingly, objects of this invention are: To provide a novel synthesis of 1-methyl-2-hydroxy-3-0xatricyclo [5.2.0.0 ]nonane; to provide a novel synthesis of 1- methyl-2-oxo-3-oxatricyclo[5.2.0.0 ]nonane; to provide novel reactions intermediate to said syntheses; and to provide novel compounds intermediate to said syntheses.

Further objects of this invention relating to the perfume and detergent arts will be apparent herein.

The above and other objects are achieved by a novel process for the synthesis of 1-methyl-2-hydroxy-3-oxatricyclo[5.2.0.0 ]nonane, which comprises (a) nitrosolyating cis-nopinol (1) to form cis-2-nopiny1 nitrite (2);

(b) irradiating the nitrite of step (a) with ultraviolet light to form 8-nitroso-cis-nopino1 dimer (3);

(c) pyrolyzing the dimer (3) of step (b) to form 8- oximino-cis-nopinol (4); and

(d) hydrolyzing the oxime (4) of step (c) to form 1- methyl-2-hydroxy-3-oxatricyclo [5.2.0.0 ]nonane (5 An optional step (e) in this process comprises oxidizing the nonane (5) to form 1-methyl-2-oxo-3-oxatricyclo [5.2.0.0 ]nonane.

The above-described process is illustrated schematically in Figure I and is disclosed in more detail in Example I, infra. Respective steps (a) through (d) involve individual reactions whose conditions are known in the art. References wherein these conditions are disclosed are summarized in Table 1. This table also shows preferred temperature conditions for each step.

3,522,276 Patented July 28, 1970 ice TABLE 1 Preferred Temperature Conditions Narrow Range Broad Rar ig, (Highly Pre- Step ierred), C. Reference (9) -30-+10 0-5 D.H.R. Barton et al.,

I. Am. Chem. 500., 82, 2640 (1960). (b)... 0-50 10-25 D0. (0)...- 70-100 -85 Do. ((1) 10-35 15-30 Do. (e) 50-100 65-75 A. Bowers et al., J. Chem Soc., 2548 (1953).

0K ONQ Step (a) a step 00 E Step (c) Step (:1)

. OH V o]\ 0 optional msssaial EXAMPLE I Synthesis of 1-methy1-2-hydroxy-3-oxatricyclo [5.2.0.0 ]nonane Step (a).--To a solution of 15.4 g. cis-nopinol (l) in 200 ml. dry pyridine was added 11.0 g. NOCl by flask to flask distillation, at 0. After an additional one hour at 0, the mixture was allowed to warm to room temperature poured into 1.5 liters water, and extracted with ether. The ether solution was washed with water, cold dilute HCl, and again with water. After drying over MgSO filtration and removal of solvent gase 18.6 g. of cis-2-nopinyl nitrite (2).

Step (b).The nitrite 2 (18.6 g.) was dissolved in 430 ml. cyclohexane, placed in a photochemical reaction flask equipped with a Vycor immersion Well, and irradiated at room temperature with a 450 watt mercury lamp (Hanovia #679A, a conventional laboratory source of ultra- In the examples herein, room temperature refers to 2026 C.

violet radiation) for 6 hours to yield, after removal of solvent, 14.2 g. of 8-notroso-cis-nopinol dimer (3).

Step (c).'The dimer 3 (14.2 g.) was dissolved in 400 ml. isopropyl alcohol and refluxed for 36 hours at 82 C. Under these conditions, 3 pyrolyzes to 4. Removal of solvent gave 10.5 g. of 8-oximino-cis-nopinol (4) which solidified on standing. Recrystallization from pentane-ether gave 4 with M.P. 1212, x 3.05 r (CH Cl and N.M.R. signals at -r8.64 (3H, singlet), 5.90 (1H, multiplet), and 2.63 (1H, singlet).

Analysis.Calcd. for C H NO (percent): C, 63.88; H, 8.94; N, 8.28. Found (percent): C, 63.95; H, 8.96; N, 8.16.

Step (d).8-oximino-cis-nopinol (4) (9.5 g.) was dissolved in 570 ml. 80% acetone-water containing 2% concentrated HCl and stirred overnight at room temperature. The solution was poured into water, extracted with ether, and the ether solution washed with saturated NaHCO and saturated NaCl, dried over MgSO filtered and stripped to 5.0 g. of 1-methyl-2-hydroxy-3-oxatricyclo[5.2.0.0 ]nonane Continuous extraction of the aqueous phase gave an additional 2.69 (87% total yield) of product, 5. Pure 5, obtained by gas chromatography, showed A 2.90 2 (no C O bond) and N.M.R. signals at r875 (3H, singlet), 8.85 (1H, doublet, J=10.8 cps), 5.28 (1H, multiplet), and 4.87 (1H, singlet). Formation of a 2,4-dinonyl phthalate derivative, M.P. 177-8" was carried out in H PO -ethanol solution.

Analysis.Calcd. for C H N O (percent): C, 53.88; H, 5.43; N, 16.76. Found (percent): C, 53.99; H, 5.51; N, 17.29.

EXAMPLE 11 Synthesis of 1-methyl-2-oxo-3-oxatricyclo [5.2.0.0 ]nonane Oxidation of 0.409 g. of 1-methyl-2-hydroxy-3-oxatri cyclo[5.2.0.0 ]nonane (5) with 0.2 g. CrO in 25 ml. acetone at 70 C. gave 0.350 g. of 1-methyl-2-oxo-3-oxatricyclo[5.2.0.0 ]nonane (6), B.P. 83-4, identified by gas-chromatographic retention time and infrared spectrum by comparison with that of authentic material prepared as described in Example VI of the aforesaid co-pending U.S. patent application of Thomas W. Gibson and William F. Erman.

EXAMPLE III Perfume compositions containing 1-methyl-2- hydroxy-3 -oxatricyclo [5 2.0.0 nonane A perfume composition was prepared by intermixing the following components.

This perfume composition exhibits a highly desirable and useful herbal bouquet odor. As discussed hereinbefore, 1 methyl-2-hydroxy-3-oxatricyc1o[5.2.0.0 ]nonane (5) is useful in various perfume compositions. Thus, the components and proportions in the perfume composition of this example can be adjusted according to methods well known in the perfume art to form a wide variety of desirable perfume compositions containing odoriferously effective amounts of 5.

EXAMPLE IV Detergent compositions A conventional heavy-duty built detergent having the following composition is prepared.

Component: Percent by weight Sodium dodecyl benzene sulfonate 20.0 Sodium tripolyphosphate 50.0 Sodium silicate 6.0 Sodium sulfate 14.0 Water 9.8

Perfume composition of Example III 0.2

This detergent composition exhibits a highly desirable herbal bouquet odor. Other perfume compositions containing odoriferously effective amounts of l-methyl-Z-hydroxy-3-oxatricyclo[5.2.0.0 ]nonane can be substituted on a weight basis for the perfume composition in the detergent composition of this example according to methods well known in the perfume art. Other detergent compositions, e.g., those disclosed in U.S. Pats. 3,159,581 and 3,213,030, can be substituted herein with satisfactory results.

EXAMPLE V Detergent bar composition A conventional household detergent bar having the following composition is prepared. Component: Percent by weight Sodium soap 75.0

Potassium soap (The total soap comprises a mixture of tallow soap and 20% coconut soap.) 7.5 Water 15.0 Perfume composition of Example 111 2.5

This detergent bar exhibits a highly desirable herbal bouquet odor. Other perfume compositions containing odoriferously effective amounts of 1-methyl-2-hydroxy-3-oxatricyclo[5.2.0.0 ]nonane can be substituted on a weight basis for the perfume composition in the detergent bar compositions of this example according to methods well known in the perfume art. Other detergent bars, e.g., those disclosed in U.S. Pats. 2,295,594, 3,066,354, and 2,407,- 649, can be substituted herein with satisfactory results.

As is apparent from the above discussion, each of the compounds 2, 3 and 4 has specific utility as an intermediate in the synthesis 5 and/or 6, which in turn exhibit highly desirable utilities based on their olfactory characteristics.

What is claimed is: 1. A process for the synthesis of 1-methyl-2-hydroxy-3- oxatricyclo[5.2.0.0 ]nonane, which comprises:

(a) nitrosolyating cis-nopinol to form cis-2-nopinyl nitrite; (b) irradiating the nitrite of step (a) with ultraviolet light to form 8-nitroso-cis-nopinol dimer; (0) pyrolyzing the dimer of step (b) to form 8-oximino-cis-nopinol; and (d) hydrolyzing the oxime of step (c) to form l-methyl-2-hydroxy-3-oxatricyclo [5.2.0.0 nonane. 2. 1-methyl-2-hydroxy-3-oxatricyclo [5 2.0.0 nonane.

References Cited Gibson et al.: Chemical Abstracts, vol. 67 (1967), 1603b, p. 1110.

ALEX MAZEL, Primary Examiner B. I. DENTZ, Assistant Examiner U.S. Cl. X.R. 

